During the last five years we have conducted a population-based epidemiologic study of Alzheimer's disease (AD) and related forms of dementia in a random sample of Medicare recipients residing in an urban multi-ethnic community. We have investigated the frequency of AD and other forms of dementia. We have investigated risk factors for AD such as apolipoprotein-E and risk modifiers such as estrogen replacement. Our study of estrogen lead to a randomized trial to prevent AD among women with a family history of AD. We examined independence in activities of daily life, and factors predicting the course and prognosis of AD. As the population of the United States ages, more racial diversity is expected. We believe that we are uniquely positioned to address many of the issues concerning aging and dementia among African-Americans, Caucasians and Hispanics. A few projects focus on biological and genetic antecedents of incident AD and dementia associated with stroke (DA). Another examines the course, prognosis and health-related consequences of AD. We will also investigate polymorphisms in regulatory sequences associated that influence APOE expression and AD risk. All projects are dependent on the Clinical Assessment Core for the identification and follow-up of a new cohort of elderly residents from the community, the Data Management and Statistical Core for data sharing and analysis and the Pathology-Molecular Genetics Core for APOE genotyping, sample storage and, when possible, postmortem confirmation of diagnoses. The Administrative Core will launch a community-wide educational program to enhance autopsy permission. The principal investigator has been involved with the project since its inception over 10 years ago. We have successful integrated advances in molecular genetics and molecular biology with traditional epidemiologic methods to emphasize our multi-disciplinary approach to the epidemiology of dementia. The questions we have proposed to address are essential for understanding who is at risk for AD and DAS and the subsequent illness impacts on function, quality of life, morbidity, mortality and finally, what strategies can be developed to intervene.